The nature of the dependence of an intracellular parasite on its host cell and the physiological relationships between host cell and parasite are the fundamental biological problems in the study of intracellular parasitism. It is proposed to attack these problems using as experimental material two different kinds of protozoan parasites of erythrocytes; (1) malaria parasites, about which much information is already available, in large part as a result of earlier work by the applicant; (2) babesias, with which very little work of a physiological nature has yet been done. Comparative studies would be done along the following three lines: (1) Extracellular cultivation and requirements for cofactors; (2) Long term intraerythrocytic culture; (3) Biosynthetic pathways, with special reference to coenzyme A, folate metabolism and purine and pyrimidine metabolism. Although a good deal is known along all three lines with malaria parasites, much more remains to be discovered. The comparative approach, using both malaria and babesia infective to man should be particularly useful in pointing toward the fundamental physiological relationships in these associations between protozoan parasites and host erythrocytes.